Heart Failure: Difference between revisions

In 1628, William Harvey first described the circulation. Little understanding of the nature of heart failure (HF) could have existed before that time. There are accounts of a disease that now would be called heart failure, and herbal medicines like the ancient boiled bulb of squill, later on the broom plant (Cytisus scoparius) and the foxglove (Digitalis purpura) were used as diuretics to treat heart failure or dropsy (edema). The latter, foxglove, was described as a diuretic by William Withering in 1785 (1). The essential glycoside substance digitalis of the leaves of the plant improves contractility of the cardiac muscle and has important parasympathetic effects, particularly on the atrioventricular node. In the 1950’s, thiazide diuretics were introduced, in the 1960’s furosemide. For a long time, diuretics and digitalis were the main treatment options for HF. After vasodilator therapy for HF was being introduced around 1960, the first randomized trial showing mortality benefit with nitrates and alphablockers for HF was published in 1986.  In 1975, the first ACE inhibitor captopril was developed and approved for human use in 1981, with a first randomized trial published in 1987. Spironolacton, introduced in 1959, was used (in low dose) for HF only after the introduction of ACE inhibitors.  Betablockers were scarcely used in heart failure when they started to be shown beneficial in the 70’s,  , but it was only in 1994 that the first randomized trial showed mortality benefit with betablockers.   

In 1948, the Framingham heart study was launched. At its start, 5209 residents of the town Framingham in the US aged between 30 and 62 were included for assessing risk factors for cardiac disease at follow up in the study which is still continued today. This study is considered the most important longitudinal source of data on the epidemiology of heart failure (2).

Heart failure patients may be broadly classified into one of two groups, or a combination of both, depending on the left ventricular ejection fraction (LVEF). The LVEF is most often assessed with echocardiography (see table 3).  When the LVEF is less than 45%, systolic pump function is abnormal and it is named systolic HF (3). If LVEF is preserved (>50%), symptoms are attributed to impaired relaxation of the heart during diastole and therefore is labeled as diastolic HF or HF with a preserved LVEF (3, 4). As a result of impaired relaxation, end diastolic pressure and subsequently left atrial- and pulmonary pressure will rise with subsequent alveolar pulmonary edema as a consequence. LF diastolic dysfunction may be present in asymptomatic patients, and it is considered an important precursor of heart failure (5). Frequently, patients have both systolic and diastolic heart failure at the same time, but the term for this ailment is still systolic heart failure.  

HF is caused by a loss of cardiac pump function which can be due to a structural abnormality of the heart muscle (e.g. myocardial infarction) or a change in the heart function (and often structure) in response to an abnormal load (e.g. aortic valve stenosis). The relationship between loading the ventricle (by filling it) and its output was described by Frank and Starling in 1918 and has become the cornerstone in understanding heart failure and how to treat it. The relationship determines that by loading the heart (increasing its filling or its pressure) the output increases (Figure 1). A heart that has a lower output can be improved by increasing its volume and its loading pressure. This is what naturally happens (LV dilatation and increased filling pressure) when the heart doesn’t pump out enough volume, and in the first phase of disease compensates for the loss of contractility. It takes more energy from the heart to work at increased loading, but the heart has a reasonable energy reserve.  In a chronic situation, remodeling of the heart progresses (by hypertrophy of myocytes and dilatation by increasing myocyte length and matrix changes), which in the long term leads to a further loss in function. The result is further increased loading pressures in the heart and by communicating the diastolic loading pressures to the left atrium and pulmonary veins, the pulmonary capillaries may become overloaded, to leak water to the lungs. That is the actual restriction towards further filling the heart as a tool to improve its function; even poor left ventricles may be filled more to increase their output (6) but the patients’ pulmonary capillaries cannot tolerate these hydrostatic pressures and start to leak water.     

[[Image:Image1.jpg|thumb|''Figure 2 Effects of decreased afterload. Red arrows indicate aortic valve opening, which occurs later and at higher LV systolic pressure when the diastolic aortic pressure is higher. Blue arrows indicate closing of the aortic valve. Bidirectional arrows represent stroke volume. When aortic pressure is decreased, stroke volume increases as a result of a lower aortic pressure during closure of the aortic valve.]]

When a patient presents with symptoms of heart failure, it is worthwhile to have a dedicated diagnostic and therapeutic plan, in the order as indicated below. (fig 3) . Clinical aspects are important for diagnosis, but the final diagnosis is only made after objective evidence of heart dysfunction.  

[[Image:Image1.jpg|thumb|Figure 3 management in heart failure.]]

Diagnosis of HF requires the simultaneous presence of at least 2 major criteria or 1 major criterion in conjunction with 2 minor criteria. The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying persons with definite congestive heart failure in an outpatient population (10).  

In general, correlation between the severity of symptoms and the severity of HF in terms of loss of maximal oxygen consumption is weak (3). The New York Heart Association functional classification is used most frequently to classify the severity of HF (Table 2). Assessing severity is needed for the proper therapy/ medication to be chosen.  

[[Image:Image1.jpg|thumb|Figure 4 flowchart suspected heart failure (3)]]

*Assess globally: are there triggers of heart failure. Hypertension, infection, anemia, rhythm disorders. Perform standard laboratory tests: in addition to hemoglobin, leukocytes, thrombocytes, creatinin, sodium and potassium levels, also liver function, thyroid function (TSH), glucose.  

*Assess ischemia: are there indications of ischemic etiology (ECG: Q’s or significant and changing ST segments, laboratory: troponins, and echocardiogram: segmental wall motion abnormality in coronary territory areas) ? If yes, then proceed with further coronary artery or myocardial perfusion imaging.  

*Are there no indications for ischemic etiology?  

#Classify phenotype of cardiomyopathy: dilated, hypertrophic, restrictive, arrhytmogenic right ventricular cardiomyopathy.

#Then assess with additional laboratory tests, including creatinin kinase, autoimmune markers, eosinophilia, ferritin and iron saturation. In some suspected cases: calcium and albumin.  

#Look for clues of etiologies: history, family history (including maternal inheritage of diabetes in a family)

#In case of fever look for infectious etiology, MRI confirmation for possible myocarditis, plasma serology.

#Look for clues on ECG: microvoltage on the ECG, AV block in combination with later atrial fibrillation. Additional lab may be warranted (monoclonal proteins in case of microvoltage in the presence of sufficient amounts of myocardium and the absence of pericardial fluid or pulmonary emphysema)  

#MRI for further classification of cardiomyopathy and assessment of presence and localization of delayed contrast enhancement

#Coronary arteriography or coronary CT scan to exclude coronary artery disease  

#Myocardial biopsy in cases where the suspicion of severe underlying disease is high (e.g. fulminant myocarditis, sarcoidosis suspicion on MRI with no other organ involved).

#Genetic testing after counseling

CHF patients should carefully monitor their body weight. A sudden increase in weight is a potential consequence of fluid retention and deterioration of HF. When patients notice a weight gain of >2kg in 3 days they should consult a physician. (Class I recommendation, level of evidence C) In obese patients (body mass index of > 30 kg/m2), weight reduction should be promoted to prevent progression of HF, decrease symptoms and improve the overall wellbeing of the patient. (Class IIa recommendation, level of evidence C) Also, attention should be paid to weight loss due to malnutrition which is frequently observed in severe HF. An altered metabolism, inflammatory mechanisms or a decreased food intake may be important factors in the pathophysiology of cardiac cachexia in HF. (Class I recommendation, level of evidence C)

[[Image:Image1.jpg|thumb|Figure 5 treatment options for patients with chronic systolic HF]]

In patients with congestive HF, total mortality and hospitalization are significantly reduced by ACE inhibitors (18).

ß-Blockade (in addition to an ACE inhibitor or ARB when ACE inhibitor is not tolerated) is indicated for every patient with symptomatic systolic HF and an EF ≤40 % (NYHA class II-IV) and in asymptomatic patients with a LVEF ≤40% after a MI . (Class I recommendation, level of evidence A)(19) Contraindications are:

 

Possible side effects include hyperkalaemia, hyponatremia, worsening renal function, and breast tenderness and/or enlargement. Eplerenon has less mastopathy side effects and is alternative to spironolacton. In patients with severe heart failure, spironolactone in addition to standard therapy, reduces morbidity and mortality (20).

[[Image:Image1.jpg|thumb|Figure 6 diuretics and site of action in the nephron.]]

[[Image:Image1.jpg|thumb|Figure 7 flowchart acute HF]]

Figure 5 offers recommendations to which patients should receive ICD treatment. In this flowchart, the timing of the placement has not been defined completely. In most patients, it should be safe to wait for their ICD whilst receiving (pharmalogical) treatment as events typically occur after 6-12 months (12). In exception to this rule, in high risk patients (i.e. patients with major myocardial infarction (MI),  extensive fibrosis on the MRI or NSVT despite optimal pharmalogical treatment), an ICD implantation should not be postponed too long. Early (within 40 days after event) ICD placement after an acute myocardial infarction has not been shown to reduce mortality, because the patients most at risk of sudden death are also the patients most at risk of death due to heart failure. (13, 14,  15). For this reason, prophylactic  ICD treatment is recommended only after 40 days in post-infarct patients who have an EF < 35%. For non-ischemic  heart failure patients, three months is considered a safe waiting time for an ICD. There are however also higher risk patients  among them, and this should be a decision made for every patient individually (16).

[[Image:Image1.jpg|thumb|Figure 8 flowchart CRT]]

When a patient has severe and progressive HF, prognosis is grim. Considering the paucity of donor hearts, the waiting list for a heart transplantation may be long and early consideration of heart transplantation is part of the treatment strategy in HF. Average 2-year survival after cardiac transplantation is approximately 80%. A patient in NYHA class III should already be investigated with an exercise test for maximal oxygen uptake, to consider further steps. Indication for heart transplantation includes a  VO2 max < 14 ml/min/kg (17). Exclusion criteria are pulmonary hypertension (risk of immediate RV donor failure), severe comorbidity, and diabetes mellitus with organ damage.  Left Ventricular Assist Devices are more commonly used as bridge to transplant when on the waiting list. They have evolved from pulsatile to continuous flow pumps, with less complications and a longer durability.  Often Left Ventricular Assist Devices become destination therapy.   

To date, no evidence exists of any treatment reducing morbidity or mortality in this patient group. With the aim to control water and sodium retention and decrease breathlessness and edema, diuretics are prescribed to HFPEF patients. Furthermore, ACE-I, Angiotensin II blockers and/or Betablockers may be considered. The CHARM trial including 3023 HF patients with preserved EF, showed angiotensin II blockade (candesartan) to have a moderate effect on hospital admission but showed no effect on risk of cardiovascular death (8).

Trials with medication illustrate that the (short term) benefit of medication is highest when the NYHA class is higher (Figure 9) (11).  

[[Image:Image1.jpg|thumb|right|300px|Figure 9 Two-year mortality in landmark contemporary clinical heart failure trials (from Cleland et al)